Estrogen and progesterone receptors are known to be valuable in predicting endocrine responsiveness and aggressiveness of breast cancers. Histochemical detection of these receptors in the heterogeneous cell populations of most tumors would offer new information on heterogeneity as well as making the receptor determination much faster and cheaper and more sensitive and also opening new possibilities for basic receptor research. We have already shown that existing histochemical receptor methods probably do not actually detect receptors. Here we propose to develop valid cytochemical receptor methods by synthesizing new more stable steroid-fluorescein conjugates and subjecting them to rigorous testing. We also propose to develop new immunocytochemical receptor methods based on specific monoclonal antibodies against the receptors themselves rather than against their ligands. Partial receptor purification by new affinity chromatography reagents will be applied to both estrogen and progesterone receptors from MCF-7 human breast cancer cells, followed by preparation of antibodies by the hybridoma technique and the use of these antibodies for receptor detection in frozen sections from breast cancer specimens.